Extracorporeal blood filtration has been in widespread use for many years, most commonly in continuous renal replacement therapies (CRRT) to treat patients suffering loss or impairment of natural kidney functions. More recently, extracorporeal blood filtration has been adapted for more general application in plasmapheresis, the purification of blood through removal of noxious components circulating in the blood plasma. Considerable interest has arisen in using plasmapheresis as a means for treating ICU patients suffering from inflammatory mediator-related diseases such as septic shock, systematic inflammatory response syndrome (SIRS), and multiple organ failure (MOF). These conditions can arise from excessive release of inflammatory mediators into the bloodstream by overstimulation of the immune system. Thus, plasmapheresis as well as other CRRT have been proposed as mechanisms for removing inflammatory mediators from the bloodstream to counteract an excessive inflammatory response. Other applications for plasmapheresis include treatment of autoimmune disorders, and treatment of severe acute pancreatitis.
In a typical hemofiltration system such as that used in plasmapheresis, blood is removed from a patient through an access site, usually by insertion of a venous catheter in a limb or central vein, and pumped through an extracorporeal circuit that includes an artificial kidney or hemofilter. The hemofilter includes a semi-permeable membrane, usually synthetic, with pore sizes selected to pass unwanted molecules. The pump provides a positive hydrostatic pressure sufficient to circulate blood along one surface of the membrane, and push water and waste products from the blood across the filter membrane and into a filtration fluid. This process, also known as ultrafiltration, causes suspended solids and solutes of high molecular weight to remain in the blood, while water and low molecular weight solutes pass through the membrane. A sterile substitution fluid, usually bicarbonate based, and having electrolyte concentrations similar to blood plasma, is added to the filtered blood to replace vital fluids and electrolytes lost through transmembrane ultrafiltration. The combined blood and substitution fluid is then returned to the patient through another venous access site.
Generally, hemofiltration is a slow continuous therapy in which sessions usually last between 12 to 24 hours. Hemofiltration processes are classified as either low-volume hemofiltration (LVH or LVHF) or high-volume hemofiltration (HVH or HVHF). The boundary between LVH and HVH is around 60 liters of ultrafiltrate per day. HVH may be administered at a rate as high as 120 liters per day.
Experimental testing suggests that certain beneficial results, e.g., higher survival rates, can be obtained from HVH, rather than LVH therapies. See, e.g., D. Journois et al., “Hemofiltration During, Cardiopulmonary Bypass in Pediatric Cardiac Surgery,” Anesthesiology Vol. 81, pp. 1181-1189 (1994); A. Grootendorst et al., “I Light-Volume Hemofiltration Improves Heterodynamics of Endotoxin-Induced Shock in the Pig,” Intensive Care Med., Vol. 18, pp. 235-240 (1992). It has been hypothesized that superior results of HVH may be attributable to its ability to more effectively remove noxious substances in the middle molecular weight range, such as cytokines, autacoids or apoptotic mediators.
However, several drawbacks exist to using HVH. For example, in order to support high volume blood flow, multiple catheters or a very large catheter may need to be installed in the patient to reduce resistance. Also, HVH requires larger, more expensive hemofilters with high flux membranes that can process fluid exchange in the 100 liter per day range. More critically, HVH must be carefully monitored to prevent complications. For example, the high-volume fluid exchange over a relatively short time period can cause hypothermia. To guard against hypothermia, the substitution fluid must be kept warm, and its temperature monitored over the course of treatment.
Although hemofiltration is known to be more efficient than other blood filtration therapies at the removal of middle molecular weight toxins, there is a lack of definitive evidence that hemofiltration prevents the onset of septic shock, SIRS, or MOF. Further research is required to advance the art of hemofiltration and demonstrate its efficacy in combating these potentially fatal complications.